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Tuesday, February 9, 2010

Show time!

This past weekend we were in Cambridge, MA, at a meeting of the advisory committee for Henry Louis Gates, Jr's next PBS series on ancestry. (A showman if there ever was one, he convened each session yelling, "Show time!") The committee includes major players in genetics, historians of the slave trade, and social scientists interested in race and ancestry. Gates himself spoke some about how much his understanding of genetics has changed since his first series, but the field, too, has changed. Much more is understood now about the nuances of ancestry testing, and how it's done.

In particular, even after just a few generations since slavery, the mixing of slaves and Europeans in North America has been such that each African American has ancestral DNA segments from populations (as represented in today's samples) from all over Africa, especially west and central Africa. They don't just have an ancestral home in one tribe or village, as has been suggested in earlier TV programs. This is something that qualified population geneticists certainly already knew, and it has to be said that the cinematic liberty of 'finding my tribe' was a disservice to education about science.

But we were particularly interested in the genetics presentations. George Church, a developer of 'next generation sequencing', the very high throughput, fast, and increasingly inexpensive means of whole genome sequencing, and now also leading the 100,000 Genome project, spoke about why he believes whole genome sequencing is important for disease prediction. The cost of sequencing continues to plummet, and he, and others at the meeting, believe that given the cost, there's no reason we shouldn't all know our personal genome within years, not decades. Gates himself and his father were both sequenced for Gates' upcoming television series, and their ancestry and disease risk (although given that Henry Louis Gates Sr is 96 1/2, they use him as a 'control', rather than to seriously consider his risk of disease) were reported at the meeting, and will be discussed on the show.

This raises many ethical issues of abuse of such data. But George believes we should stop pretending that there can be complete confidentiality of such data, or that there may not be abuses. He says that since we can't stop that formally, we'll need to use societal mechanisms--laws, shame, etc. But meanwhile, let's get the data out there for anyone to analyze, Wikipedia-like, and that way anyone with new ideas can get them expressed.

It was interesting to be in the same room with multiple people who actually have their genome on a disk, something that was pure sci-fi fantasy just a few years ago. We had dinner, e.g., with PGP4 (the fourth person sequenced in Church's Personal Genome Project). He has blogged about, and is now writing a book about the experience. One requirement of all participants in the project is that they allow all their data, including medical records, to be in the public domain. Church also goes beyond informed consent; participants must get 100% on a genetics test, showing that they understand what their sequence will tell them, as well as any risks -- which Church says are unknown, and can't be guaranteed against.

Twelve of the anticipated 100,000 PGP volunteers have now been sequenced. That leaves a lot to go, but there are at least 15,000 volunteers, including people at the meeting, currently undergoing the screening process, so they expect, once the project has more money in hand, that the pace will pick up. You, too, can sign up.

But not everyone is eager to be sequenced. David Altshuler, for example, a physician and diabetes researcher, with a pretty hefty history of gene searching under his belt, has no interest. He said, in his presentation, that it would be like healthy people getting whole body CT scans, or x-rays, a futile exercise. In large part, his objection is that it's nearly impossible to predict risk. Further, he has no interest in 'personalized genomic medicine'. He sees no point in tailoring drugs to individuals, the modern promise of genetics, and now of the NIH with Francis Collins at the head, and would much rather see drug companies designing drugs that would work for the masses. He knows, and agrees (and other presentations made the point) that there certainly is a growing list of high-risk genetic variants, and those can be worth routinely identifying (though he mentioned the fact that we don't really know how many of us are walking around with 'disease' genotypes but are perfectly healthy--and it's likely often to be a high percent of unaffected carriers).

In the debate about GWAS and personalized medicine, David's talk was one of the most restrained, responsible, and reasoned presentations we've heard in a long time. He presented reasons why we cannot expect too much (things we've blogged and written about frequently), and he gave a clinician's point of view.

There may be an emerging consensus: there are lots of genes with some allele or other that confers meaningful risk. Thousands of rare diseases may be due in large part to such alleles. But most cases of complex diseases are likely to remain that way--complex at the individual level--and the challenge is to find ways to attack these in a general way.

As to ancestry, there's still a big gulf between the perspective of social scientists, who largely still do not quite grasp the genetic messages, and the geneticists who still do not grasp the issues the social scientists are concerned about. Gates' television series help to promote enthusiasm for searching for identity through ancestry, and interest in genetics in this context. Hopefully, this can also have beneficial effects on society that involve genetics in responsible ways that the social scientists in this area can be enthusiastic about.

9 comments:

Great post! Every time I imagine getting my whole genome analyzed, I remember back to looking at my knee x-rays when I was 16 and the doctor saying to a young (injured) 5'7" point guard with college hoop dreams, "Well, you're all done growing! Your growth plates are fused. This is as tall as you're going to get!" I was absolutely horrified to have the case closed on a basically lifelong mystery, especially one that was drenched in so much hope. I think I'd like to keep my complex trait/disease alleles in the mystery category for as long as possible.

There is a BIG SECRET Nature paper about to be released, with as much hoopla and hype as you can imagine, that raises important issues about complete disclosure and the history in anthropology of make value judgments. I can't say any more at present, but I think this will burst on the scene next week perhaps.

Thanks, Holly! And, of course, the doctor who looked at your x-rays, and dashed your hopes, actually had solid evidence to predict that you had reached your adult height. In general, except for rare Mendelian disorders, predicting risk from genetic evidence is much iffier. And what would one do with the information, anyway? "Moderation in all things" is pretty good advice, with or without your genome on a disk.

The shows approach accuracy, each series more responsible and better than its predecessors. Even Skip recognizes the past issues and is making efforts to improve each time, without sacrificing the "Show time" human-interest aspect of his work

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